Hasil untuk "Neoplasms. Tumors. Oncology. Including cancer and carcinogens"

Yong Wang, Jia-yu Wu, Qian Xiang et al.

Background and aimEntecavir (ETV) and tenofovir disoproxil fumarate (TDF) are first-line antiviral treatment methods for chronic hepatitis B virus (HBV) infection. However, the different effects of TDF versus ETV on the prognosis of HBV-related hepatocellular carcinoma (HCC) after surgical resection remain controversial. We conducted this meta-analysis to assess the differences of TDF versus ETV in recurrence and survival for HBV-related HCC after liver resection.MethodsWe searched MEDLINE, EMBASE, PubMed and Web of Science for the related studies published before January 2025. Meta-analysis was performed by use of a random-effects model.ResultsA total of 15 studies were included in this meta-analysis. The pooled results showed that TDF was associated with better recurrence-free survival (RFS) (HR= 0.79, 95% CI 0.70-0.88) and lower risk of recurrence (HR=0.73, 95% CI 0.62-0.86) than ETV in HBV-related HCC patients after surgical resection. Further analysis indicated that TDF reduced the risk of late recurrence (HR= 0.70, 95% CI 0.55-0.88) rather than early recurrence (HR= 1.00, 95% CI 0.85-1.17) compared with ETV. Also, the pooled results revealed that TDF was associated with better overall survival (OS) (HR= 0.55, 95% CI 0.41-0.74) and lower risk of overall mortality (HR= 0.55, 95% CI 0.41-0.74) than ETV.ConclusionThis meta-analysis provided evidence that TDF has better benefits in improving survival and reducing late recurrence than ETV in HBV-related HCC patients after surgical resection.

Iwona U. Dębosz-Suwińska, Dawid Bodusz, Barbara Bekman et al.

INTRODUCTION: Online adaptive radiotherapy (oART) is an innovative approach that allows a treatment plan tobe adjusted accurately and precisely on a daily basis according to changes in tumour and normal tissues duringtreatment courses. MATERIAL AND METHODS: The publication will focus on the presentation and subsequent stages of treatmentplanning, as well as their implementation, using the example of a patient with prostate cancer treated at ourinstitution. The patient underwent hypofractionated radiotherapy with a daily fraction dose of 7.25 Gy to a totaldose of 36.25 Gy. RESULTS: The median time required for the adaptation workflow (AT) was 29 min (SD 5 min). The mean bladdervolume measured in the cone beam computed tomography (CBCT) images done before treatment was 184 cm3and ranged from 146 cm3 to 203 cm3. For comparison, the blader volume at baseline computed tomography (CT)was 238 cm3. The mean rectal volume during treatment was 82 cm3 and ranged from 70cm3 to 100 cm3 and wasalso less than at baseline CT (122 cm3). The observed differences in patient geometry influenced changes in dosedistribution in the planning target volume (PTV) and clinical target volume (CTV). In an extreme case (the fourthfraction of treatment), the patient treated according to the scheduled treatment plan would receive 99% (7.18 Gy)and 98% (7.11 Gy) of the prescribed dose only in 49% of CTV and 48% of PTV, respectively. The adaptation processimproved dose distribution to cover 100% of the PTV and CTV to at least 98% and 99% respectively of the prescribeddose during each fraction of treatment. CONCLUSIONS: The example shown presented very high interfractional mobility. The use of oART allowed for adjustmentto those changes, ensuring proper coverage of the CTV and PTV with the therapeutic dose during eachtreatment fraction.

Sandrine Grossetete, Sakina Zaidi, Martin F. Orth et al.

Abstract Ewing sarcoma is an aggressive bone tumor of adolescence characterized by a hallmark EWSR1::ETS fusion oncogene. The resulting chimeric oncoprotein drives tumorigenesis by reshaping transcriptional and epigenetic landscapes. However, how it is transcriptionally regulated and whether additional master transcription factors (MTFs) form a core regulatory circuit (CRC) in Ewing sarcoma remain unclear. Using an extensive panel of Ewing sarcoma cell lines and primary tumors, we mapped super-enhancers and identified enrichment of GGAA microsatellites, confirming their specificity to Ewing sarcoma as compared to other pediatric cancers and normal tissues. Integrating transcriptomic, epigenetic, 3D chromatin conformation, and dependency data, we predicted a set of MTFs potentially forming a CRC. However, functional validation demonstrated that these MTFs neither establish auto-regulatory loops nor confer robust proliferative dependencies typical of CRCs in other pediatric tumors. Instead, EWSR1::FLI1 emerged as an “hegemonic” oncoprotein, regulating expression of these MTFs without reciprocal regulation. Knockdown of EWSR1::FLI1 strongly shifted H3K27ac profiles toward mesenchymal states, whereas silencing individual or combined MTFs did not alter cell growth or EWSR1::FLI1 expression. These findings highlight the absence of a classical CRC in Ewing sarcoma and emphasize EWSR1::FLI1 as the dominant oncoprotein and a major vulnerability in this disease.

Constance Bordet, Mahmoud Zureik, Yoann Zelmat et al.

Introduction: Previous studies have identified an interaction between protein kinase inhibitors (PKIs) and proton pump inhibitors (PPIs) in patients with lung cancer. This type of interaction may reduce the efficacy of PKIs. However, the effect of PKI-PPI interaction on patient mortality remains controversial. This study set out to determine the impact of PKI-PPI interaction on overall survival for lung cancer patients. Materials and methods: This study was conducted using data from the French National Health Care Database from January 1, 2011 to December 31, 2021. We identified patients with: (i) an age equal to or greater than 18 years; (ii) lung cancer; and (iii) at least one reimbursement for one of the following drugs: erlotinib, gefitinib, afatinib and osimertinib. Patients were followed-up between the first date of PKI reimbursement and either December 31, 2021 or if they died, the date on which death occurred. The cumulative exposure to PPI duration during PKI treatment was calculated as the ratio between the number of concomitant exposure days to PKI and PPI and the number of exposure days to PKI. A survival analysis using a Cox proportional hazards model was then performed to assess the risk of death following exposure to a PKI-PPI interaction. Results: 34,048 patients received at least one reimbursement for PKIs of interest in our study: 26,133 (76.8 %) were exposed to erlotinib; 3,142 (9.2 %) to gefitinib; 1,417 (4.2 %) to afatinib; and 3,356 (9.9 %) to osimertinib. Patients with concomitant exposure to PKI-PPI interaction during 20 % or more of the PKI treatment period demonstrated an increased risk of death (HR, 1.60 [95 % CI, 1.57–1.64]) compared to other patients. When this cut-off varied from 10 % to 80 %, the estimated HR ranged from 1.46 [95 % CI, 1.43–1.50] to 2.19 [95 % CI, 2.12–2.25]. Discussion/Conclusion: In our study, an elevated risk of death was observed in patients exposed to PKI-PPI interaction. Finally, we were able to identify a dose-dependent effect for this interaction. This deleterious effect of osimertinib and PPI was revealed for the first time in real life conditions.

Mingyang He, Xin Wang, Dongbin Wang et al.

BackgroundPrevious observational studies regarding the relationship between acne and prostate cancer have reported inconsistent results. As such studies are prone to biases, we conducted this Mendelian randomization (MR) analysis to better explore the causal association between acne and prostate cancer.MethodsThe genetic data for assessing acne were acquired from the largest genome-wide association study (GWAS) of acne by far, and the genetic data for assessing prostate cancer were acquired from the FinnGen consortium, UK Biobank, European Bioinformatics Institute, and IEU OpenGWAS project. We performed two-sample MR analyses using data from these GWASs followed by a meta-analysis to provide an overall evaluation. The primary MR methods used included inverse variance weighted, MR-Egger, and weighted median. Leave-one-out sensitivity tests, Cochran’s Q tests, and MR-Egger intercept tests were used to bolster the robustness of the MR results.ResultsThrough MR combined with meta-analysis, our study found no genetic causal relationship between acne and prostate cancer (p=0.378; odds ratio=0.985; 95% confidence interval, 0.954–1.018). Sensitivity tests ensured the robustness of this result.ConclusionAcne should not be considered as a morbidity hazard factor for prostate cancer.

Bilan Yang, Xiaoli Xi, Hongsheng Yu et al.

Abstract Background The optimal treatment strategy for early‐stage hepatocellular carcinoma (HCC) remains controversial, specifically in regard to surgical resection (SR) and ablation. The aim of this study was to investigate the impact of SR and ablation on recurrence and prognosis in early‐stage HCC patients, to optimize treatment strategies and improve long‐term survival. Methods A retrospective analysis was conducted on 801 patients diagnosed with Barcelona Clinic Liver Cancer (BCLC) stage 0/A HCC and treated with SR or ablation between January 2015 and December 2019. The effectiveness and complications of both treatments were analyzed, and patients were followed up to measure recurrence and survival. Propensity score matching (PSM) was employed to increase comparability between the two groups. The Kaplan–Meier method was used to analyze recurrence and survival, and a Cox risk proportional hazard model was used to identify risk factors that affect recurrence and surviva. Results Before PSM, the overall survival (OS) rates were similar in both groups, with recurrence‐free survival (RFS) rates better in the SR group than in the ablation group. After PSM, there was no significant difference in OS between the two groups. However, the RFS rates were significantly better in the SR group than in the ablation group. The ablation group exhibited superior outcomes compared to the SR group, with shorter treatment times, reduced bleeding, shorter hospital stays, and lower hospital costs. Concerning the location of the HCC within the liver, comparable efficacy was observed between SR and ablation for disease located in the noncentral region or left lobe. However, for HCCs located in the central region or right lobe of the liver, SR was more effective than ablation. Conclusions This study revealed no significant difference in OS between SR and ablation for early‐stage HCC, with SR providing better RFS and ablation demonstrating better safety profiles and lower hospital costs. These findings offer valuable insights for clinicians in determining optimal treatment strategies for early‐stage HCC patients, particularly in terms of balancing efficacy, safety, and cost considerations.

Hui Luo, Jing Jin, Jiajia Jin et al.

Abstract Extracellular vesicles (EVs) have tremendous potential as nano/micron-sized drug delivery carriers. Their physical, chemical and biological characteristics distinguish them as unique carriers with specific pharmacokinetic, circulating metabolic, and biodistribution patterns in the delivery of therapeutic cargoes. They are critical mediators in the pathology of many diseases, including inflammatory diseases, fibrosis, and cancer, but they are also essential mediators in immunomodulation, cancer treatment, infectious defense, and tissue repair. In this review, we emphasize recent advances in oncology therapy using macrophage EVs, mesenchymal stem cell EVs, milk EVs, and plant EVs, as well as the advantages of EVs as delivery platforms and their prospective clinical applications and use.

Qirui Chen, Yan Liu, Yi Liu et al.

Abstract Background To investigate the effect of continuous oral aspirin in perioperative period on bleeding in pneumonectomy. Methods A total of 170 patients who underwent pneumonectomy in our hospital from March 2021 to March 2022 were selected as the study objects. All patients took oral aspirin before surgery and did not take other antiplatelet agent or anticoagulants at the same time. The continuation group included 85 cases and continued to take aspirin 100 mg/day during the perioperative period, and the interruption group included 85 cases who stopped aspirin for 7 days before surgery and 3 days after surgery, without bridging therapy. The intraoperative blood loss, operation time, conversion to thoracotomy rate, postoperative bleeding rate, blood transfusion rate, thrombotic events, postoperative drainage volume, length of hospital stay, and total hospital cost of the two groups were compared. Results There were no statistically significant differences in intraoperative blood loss, operative time, rate of conversion to open, postoperative drainage, hospital stay, and cost between the two groups (p > 0.05), and there were no reoperations due to bleeding between the two groups. Conclusions Aspirin should be continued throughout the perioperative period in all high‐risk patients requiring pneumonectomy after balancing ischemic‐bleeding risks.

A. Vera- Rosas, D. Aguiar, A. Domínguez et al.

Background/purpose: The aim of this study is to assess for the first time the immediate and long term impact on quality-of-life of HBO treatments(HBOT) at 1.45 ATA (Absolute Atmospheric Pressure) Medical Hyperbaric chamber. Methods: Patients over 18 years-old, suffering of grade 3 Common Terminology Criteria for Adverse Events (CTCAE) 4.0 radiation induced late toxicity and progressing to standard support therapy were included in this prospective study. HBOT was given daily, sixty minutes per session by a Medical Hyperbaric Chamber Biobarica System at 1.45 ATA at 100% O2. Forty sessions were prescribed for all patients given in 8 weeks. Patients reported outcomes (PROs) was assessed by the QLQ-C30 questionnaire, before starting, in the last week of the treatment, as well as during follow up. Results: Between February-2018/June-2021, 48 patients fulfilled the inclusion criteria. A total of 37 patients (77%) completed the treatment prescribed HBOT sessions. Patients with anal fibrosis (9/37) and brain necrosis (7/37) were the most frequently treated. The most common symptoms were pain (65%) and bleeding (54%). In addition, thirty out of the 37 patients who completed the pre- and post-treatment Patients Reported Outcomes (PROs) assessment also completed the follow up European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire C30 (EORTC-QLQ-C30), and were evaluated in the present study. Mean follow up was 22,10 (6–39) months.The Median score of the EORTC-QLQ-C30, at the end of HBOT and during follow-up, was improved in all assessed domains, except in the cognitive aspect (p = 0.106). Conclusions: HBOT at 1.45 ATA is a feasible and well tolerated treatment, improving long term quality of life in terms of physical function, daily activities and general health subjective state of patients suffering severe late radiation-induced toxicity.

Ruxian Tian, Yumei Li, Chuanliang Jia et al.

ObjectiveWe aim to establish and validate computed tomography (CT)-based radiomics model for predicting TP53 status in patients with laryngeal squamous cell carcinoma (LSCC).MethodsWe divided all patients into a training set 1 (n=66) and a testing set 1 (n=30) to establish and validate radiomics model to predict TP53. Radiomics features were selected by analysis of variance (ANOVA) and the least absolute shrinkage and selection operator (Lasso) regression analysis. Five radiomics models were established by using K-Nearest Neighbor, logistics regressive, linear-support vector machine (SVM), gaussian-SVM, and polynomial-SVM in training set 1. We also divided all patients into a training set 2 and a testing set 2 according to different CT equipment to establish and evaluate the stability of the radiomics models.ResultsAfter ANOVA and subsequent Lasso regression analysis, 22 radiomics features were selected to build the radiomics model in training set 1. The radiomics model based on linear-SVM has the best predictive performance of the five models, and the area under the receiver operating characteristic curve in training set 1 and testing set 1 were 0.831(95% confidence interval [CI] 0.692–0.970) and 0.797(95% CI 0.632–0.957) respectively. The specificity, sensitivity, and accuracy were 0.971(95% CI 0.834–0.999), 0.714(95% CI 0.535–0.848), and 0.843(95% CI 0.657–0.928) in training set 1 and 0.750(95% CI 0.500–0.938), 0.786(95% CI 0.571–1.000), and 0.667(95% CI 0.467–0.720) in testing set 1, respectively. In addition, the radiomics model also achieved stable prediction results even in different CT equipment. Decision curve analysis showed that the radiomics model for predicting TP53 status could benefit LSCC patients.ConclusionWe developed and validated a relatively optimal radiomics model for TP53 status prediction by trying five different machine learning methods in patients with LSCC. It shown great potential of radiomics features for predicting TP53 status preoperatively and guiding clinical treatment.

Marius W. Baeken, Mario Schwarz, Andreas Kern et al.

Abstract The sirtuin (SIRT) protein family has been of major research interest over the last decades because of their involvement in aging, cancer, and cell death. SIRTs have been implicated in gene and metabolic regulation through their capacity to remove acyl groups from lysine residues in proteins in an NAD+-dependent manner, which may alter individual protein properties as well as the histone–DNA interaction. Since SIRTs regulate a wide range of different signaling cascades, a fine-tuned homeostasis of these proteins is imperative to guarantee the function and survival of the cell. So far, however, how exactly this homeostasis is established has remained unknown. Here, we provide evidence that neuronal SIRT degradation in Parkinson’s disease (PD) models is executed by autophagy rather than the proteasome. In neuronal Lund human mesencephalic (LUHMES) cells, all seven SIRTs were substrates for autophagy and showed an accelerated autophagy-dependent degradation upon 1-methyl-4-phenylpyridinium (MPP+) mediated oxidative insults in vitro, whereas the proteasome did not contribute to the removal of oxidized SIRTs. Through blockade of endogenous H2O2 generation and supplementation with the selective radical scavenger phenothiazine (PHT), we could identify H2O2-derived species as the responsible SIRT-oxidizing agents. Analysis of all human SIRTs suggested a conserved regulatory motif based on cysteine oxidation, which may have triggered their degradation via autophagy. High amounts of H2O2, however, rapidly carbonylated selectively SIRT2, SIRT6, and SIRT7, which were found to accumulate carbonylation-prone amino acids. Our data may help in finding new strategies to maintain and modify SIRT bioavailability in neurodegenerative disorders.

Jane-Chloe Trone, Alexis Vallard, Sandrine Sotton et al.

Abstract Background Glioblastoma multiforme (GBM) has a poor prognosis despite a multi modal treatment that includes normofractionated radiotherapy. So, various hypofractionated alternatives to normofractionated RT have been tested to improve such prognosis. There is need of systematic review and meta-analysis to analyse the literature properly and maybe generalised the use of hypofractionation. The aim of this study was first, to perform a meta-analysis of all controlled trials testing the impact of hypofractionation on survival without age restriction and secondly, to analyse data from all non-comparative trials testing the impact of hypofractionation, radiosurgery and hypofractionated stereotactic RT in first line. Materials/Methods We searched Medline, Embase and Cochrane databases to identify all publications testing the impact of hypofractionation in glioblastoma between 1985 and March 2020. Combined hazard ratio from comparative studies was calculated for overall survival. The impact of study design, age and use of adjuvant temozolomide was explored by stratification. Meta-regressions were performed to determine the impact of prognostic factors. Results 2283 publications were identified. Eleven comparative trials were included. No impact on overall survival was evidenced (HR: 1.07, 95%CI: 0.89-1.28) without age restriction. The analysis of non-comparative literature revealed heterogeneous outcomes with limited quality of reporting. Concurrent chemotherapy, completion of surgery, immobilization device, isodose of prescription, and prescribed dose (depending on tumour volume) were poorly described. However, results on survival are encouraging and were correlated with the percentage of resected patients and with patients age but not with median dose. Conclusions Because few trials were randomized and because the limited quality of reporting, it is difficult to define the place of hypofactionation in glioblastoma. In first line, hypofractionation resulted in comparable survival outcome with the benefit of a shortened duration. The method used to assess hypofractionation needs to be improved.

Simone Mocellin

Simone Mocellin

Simone Mocellin

Simone Mocellin

Simone Mocellin

Mana Mann, Philip J. Landrigan

Simone Mocellin